Cigarette smokers constitute the largest population exposed to environmental mutagens and the largest population of drug abusers. Controlled, prospective studies have been designed to directly and indirectly detect mutagens in urine and blood of smokers and to determine if there is a genetic response to exposure to mutagens in cigarette smoke. Urine samples will be concentrated and assayed by the Ames procedure. Sister chromatid exchange, unscheduled DNA synthesis and chromosomal analysis will be performed on short term lymphocyte cultures. The results of Ames and the various cytogenetic assays will be compared to determine the relative effectiveness of the different assay systems. Results of these studies will yield meaningful data on the effectiveness of various assay systems to detect mutagenic activity in body fluids, and the role of host response to standard doses of mutagens in cigarette smoke. Procedures developed in this study will have practical application to assays for mutagens other than cigarettes.